This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Age-related macular degeneration (AMD) is the leading cause of vision loss in adults over 60 years of age. The macula, the specialized area of the retina that underlies sharp central vision, is present only in human and nonhuman primates, so that only nonhuman primates can provide an accurate model for this complex disease. Other common inherited retinal diseases such as retinitis pigmentosa and Usher syndrome do not selectively affect the macula, but in these diseases also, a nonhuman primate model would be uniquely valuable for understanding the factors involved in preservation of the macula and central vision, a primary therapeutic goal. Availability of a nonhuman primate model of AMD would make possible tests of several promising therapeutic approaches, including gene therapy, retinal transplantation, growth factors and nutritional interventions, as well as studies of the mechanisms underlying retinal degeneration. This project's objective is to develop a nonhuman primate model for AMD using several complementary approaches: 1) identifying monkeys with naturally-occurring macular disease in the ONPRC macaque colonies;2) determining the genetic mutations or susceptibility factors and gene expression changes underlying this disease;3) testing the feasibility, safety and efficacy of retinal gene therapies;and 4) testing the effects of long-term, controlled dietary interventions that may protect the macula from macular degeneration.